期刊
SCIENCE
卷 329, 期 5997, 页码 1348-1353出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1192049
关键词
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资金
- Jackson laboratory
- European Community
- Cancer Research UK
- Wellcome Trust
- Herchel Smith Fellowship
- Novo Nordisk Foundation
- Cancer Research UK [11224] Funding Source: researchfish
SIRT6 belongs to the sirtuin family of protein lysine deacetylases, which regulate aging and genome stability. We found that human SIRT6 has a role in promoting DNA end resection, a crucial step in DNA double-strand break (DSB) repair by homologous recombination. SIRT6 depletion impaired the accumulation of replication protein A and single-stranded DNA at DNA damage sites, reduced rates of homologous recombination, and sensitized cells to DSB-inducing agents. We identified the DSB resection protein CtIP [C-terminal binding protein (CtBP) interacting protein] as a SIRT6 interaction partner and showed that SIRT6-dependent CtIP deacetylation promotes resection. A nonacetylatable CtIP mutant alleviated the effect of SIRT6 depletion on resection, thus identifying CtIP as a key substrate by which SIRT6 facilitates DSB processing and homologous recombination. These findings further clarify how SIRT6 promotes genome stability.
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